5OLM

TRIM21

5OLM の概要

• エントリーDOI: 10.2210/pdb5olm/pdb
• 分子名称: E3 ubiquitin-protein ligase TRIM21, ZINC ION (3 entities in total)
• 機能のキーワード: antibody, antiviral protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P19474
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30101.55

構造登録者

James, L.C. (登録日: 2017-07-28, 公開日: 2018-04-25, 最終更新日: 2024-05-08)

主引用文献

Dickson, C.,Fletcher, A.,Vaysburd, M.,Yang, J.C.,Mallery, D.L.,Zeng, J.,Johnson, C.M.,McLaughlin, S.H.,Skehel, M.,Maslen, S.,Cruickshank, J.,Huguenin-Dezot, N.,Chin, J.W.,Neuhaus, D.,James, L.C.
Intracellular antibody signalling is regulated by phosphorylation of the Fc receptor TRIM21.
Elife, 7:-, 2018

PubMed Abstract: Cell surface Fc receptors activate inflammation and are tightly controlled to prevent autoimmunity. Antibodies also simulate potent immune signalling from inside the cell via the cytosolic antibody receptor TRIM21, but how this is regulated is unknown. Here we show that TRIM21 signalling is constitutively repressed by its B-Box domain and activated by phosphorylation. The B-Box occupies an E2 binding site on the catalytic RING domain by mimicking E2-E3 interactions, inhibiting TRIM21 ubiquitination and preventing immune activation. TRIM21 is derepressed by IKKβ and TBK1 phosphorylation of an LxxIS motif in the RING domain, at the interface with the B-Box. Incorporation of phosphoserine or a phosphomimetic within this motif relieves B-Box inhibition, promoting E2 binding, RING catalysis, NF-κB activation and cytokine transcription upon infection with DNA or RNA viruses. These data explain how intracellular antibody signalling is regulated and reveal that the B-Box is a critical regulator of RING E3 ligase activity.

PubMed: 29667579
DOI: 10.7554/eLife.32660

実験手法

X-RAY DIFFRACTION (1.95 Å)